GOALI: Informing Amorphous Formulations Design through Quantitative Nonlinear Optical Analysis

目标：通过定量非线性光学分析为非晶配方设计提供信息

• 批准号: 1412888
• 负责人: Garth Simpson
• 金额: $ 48万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412888&HistoricalAwards=false
• 关键词: GOALI; Informing; Amorphous; Formulations; Design

Even trace crystallinity can profoundly affect the physical behavior of materials ranging from pharmaceutical ingredients to confectionaries. However, detection of low levels of crystallinity for small organic molecules like active pharmaceutical ingredients is notoriously challenging with existing benchtop instruments. In this project supported by the Chemical Measurement and Imaging Program of the Division of Chemistry, Professor Garth Simpson, his research group at Purdue University, and their industrial partner Merck & Co., Inc., will develop a new approach for crystal detection and quantification, based on nonlinear optical light-matter interaction. In sufficiently intense optical fields such as those arising in the focus of a femtosecond pulsed laser, normally weak interactions that scale nonlinearly with the intensity become significant. These new effects provide contrast in microscopy that is highly selective for crystals of small chiral molecules. Quantitative second harmonic generation (SHG) microscopy instrumentation incorporating real-time data processing will be developed and applied for characterizing trace crystallinity at parts-per-million (ppm) levels, representing a 10,000-fold reduction in the lower limits of detection relative to existing common benchtop methods. Independent confirmation of trace crystal detection and percent crystallinity determination will be performed using a one-of-a-kind instrument integrating SHG microscopy and synchrotron X-ray diffraction. Initial applications will target analysis of amorphous formulations through collaborations between Purdue investigators and researchers at Merck. Partnering with Merck will help span the"valley of death" - obstacles that prevent drug discoveries transition to new drugs - to align fundamental discoveries on the nonlinear optics of chiral systems with the realities of private sector applications. If successful, the development of reliable benchtop tools for trace crystal detection could directly impact the design and quality control of drug formulations and potentially inform analyses of a significantly broader scope of biological materials.

即使是微量结晶度也会深刻影响从药物成分到糖果等材料的物理行为。然而，利用现有的台式仪器检测活性药物成分等有机小分子的低结晶度是众所周知的挑战。在这个由化学系化学测量和成像项目支持的项目中，加思·辛普森教授及其在普渡大学的研究小组及其工业合作伙伴默克公司将开发一种用于晶体检测和定量的新方法，基于非线性光学光-物质相互作用。在足够强的光场中，例如飞秒脉冲激光焦点中产生的光场，通常随强度非线性变化的弱相互作用变得显着。这些新效应提供了对小手性分子晶体具有高度选择性的显微镜对比度。将开发并应用结合实时数据处理的定量二次谐波发生 (SHG) 显微仪器，用于表征百万分之一 (ppm) 水平的痕量结晶度，这意味着相对于现有的检测下限降低了 10,000 倍常见的台式方法。将使用集成 SHG 显微镜和同步加速器 X 射线衍射的独一无二的仪器来独立确认痕量晶体检测和百分比结晶度测定。最初的应用将通过普渡大学研究人员和默克研究人员之间的合作来分析无定形制剂。与默克的合作将有助于跨越“死亡之谷”——阻碍药物发现过渡到新药的障碍——使手性系统非线性光学的基本发现与私营部门应用的现实相一致。如果成功，用于痕量晶体检测的可靠台式工具的开发可能会直接影响药物配方的设计和质量控制，并可能为更广泛的生物材料的分析提供信息。